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Genetically engineered MRI-visible phages enable the noninvasive detection of bacteria in deep tissues with tunable cell-type specificity.

Clear cell renal cell carcinoma (CC-RCC) remains one of the most deadly forms of kidney cancer despite recent advancements in targeted therapeutics, including tyrosine kinase and immune checkpoint inhibitors. Unfortunately, these therapies have not been able to show better than a 16% complete response rate. In this study we evaluated a cyclin-dependent kinase inhibitor, Dinaciclib, as a potential new targeted therapeutic for CC-RCC. In vitro, Dinaciclib showed anti-proliferative and pro-apoptotic effects on CC-RCC cell lines in Cell Titer Glo, Crystal Violet, FACS-based cell cycle analysis, and TUNEL assays. Additionally, these responses were accompanied by a reduction in phospho-Rb and pro-survival MCL-1 cell signaling responses, as well as the induction of caspase 3 and PARP cleavage. In vivo, Dinaciclib efficiently inhibited primary tumor growth in an orthotopic, patient-derived xenograft-based CC-RCC mouse model. Importantly, Dinaciclib targeted both CD105+ cancer stem cells (CSCs) and CD105- non-CSCs in vivo. Moreover, normal cell lines, as well as a CC-RCC cell line with re-expressed von-Hippel Lindau (VHL) tumor suppressor gene, were protected from Dinaciclib-induced cytotoxicity when not actively dividing, indicating an effective therapeutic window due to synthetic lethality of Dinaciclib treatment with VHL loss. Thus, Dinaciclib represents a novel potential therapeutic for CC-RCC.

Triple-negative breast cancer (TNBC) is notoriously aggressive with high metastatic potential, which has recently been linked to high rates of fatty acid oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation in TNBC through the prometastatic protein, CUB-domain containing protein 1 (CDCP1). We show that a "low-lipid" phenotype is characteristic of breast cancer cells compared with normal breast epithelial cells and negatively correlates with invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two-photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and increased lipid utilization in the mitochondria through FAO, fueling oxidative phosphorylation. These findings are supported by CDCP1's interaction with and inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1 knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1 knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In vivo, inhibiting CDCP1 activity with an engineered blocking fragment (extracellular portion of cleaved CDCP1) lead to increased LD abundance in primary tumors, decreased metastasis, and increased ACSL activity in two animal models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their corresponding primary tumors, indicating that LD abundance in primary tumor might serve as a prognostic marker for metastatic potential. Our studies have important implications for the development of TNBC therapeutics to specifically block CDCP1-driven FAO and oxidative phosphorylation, which contribute to TNBC migration and metastasis.

Landslides recurrently cause severe damage and, in some cases, the full disruption of many highways in mountainous areas, which can last from a few days to even months. Thus, there is a high demand for monitoring tools and precipitation data to support highway alignment selections before construction. In this study, we proposed a new system highway alignment selection method based on coherent scatter InSAR (CSI) and ~1 km high-spatial-resolution precipitation (HSRP) analysis. Prior to the CSI, we calculated and analyzed the feasibility of Sentinel-1A ascending and descending data. To illustrate the performance of the CSI, CSI and SBAS–InSAR were both utilized to monitor 80 slow-moving landslides, which were identified by optical remote-sensing interpretation and field investigation, along the Barkam–Kangting Highway Corridor (BKHC) in southwestern China, relying on 56 Sentinel-1A descending images from September 2019 to September 2021. The results reveal that CSI has clearer deformation signals and more measurement points (MPs) than SBAS-InSAR. And the maximum cumulative displacements and rates of the landslides reach −75 mm and −64 mm/year within the monitoring period (CSI results), respectively. Furthermore, the rates of the landslides near the Jinchuan River are higher than those of the landslides far from the river. Subsequently, to optimize the highway alignment selection, we analyzed the spatiotemporal evolution characteristics of feature points on a typical landslide by combining the −1 km HSRP, which was calculated from the 30′ Climatic Research Unit (CRU) time-series datasets, with the climatology datasets of WorldClim using delta spatial downscaling. The analysis shows that the sliding rates of landslides augment from the back edge to the tongue because of fluvial erosion and that accelerated sliding is highly related to the intense precipitation between April and September each year (ASP). Consequently, three solution types were established in our method by setting thresholds for the deformation rates and ASPs of every landslide. Afterward, the risk-optimal alignment selection of the BKHC was finalized according to the solution types and consideration of the construction's possible impacts. Ultimately, the major problems and challenges for our method were discussed, and conclusions were given. [ABSTRACT FROM AUTHOR]